Process for preparing rifaximin κ

Abstract

The present invention relates to a process for obtaining rifaximin κ comprising the following steps: a) reacting rifamycin O with 2-amino-4-picoline in the presence of a solvent mixture comprising water and a solvent selected from methyl isobutylketone, ethylacetate and a water soluble solvent; b) obtaining a rifaximin solution by removing the aqueous phase; c) obtaining rifaximin κ from the rifaximin solution, wherein when the solvent is a water soluble solvent, either methyl isobutylketone or ethylacetate is further added in step a). In another aspect the process of the invention relates to a process for obtaining the crystalline form κ of rifaximin comprising the following steps: i) contacting rifaximin or a rifaximin solution with exclusively ethylacetate, ii) obtaining the rifaximin in crystalline form κ by removing ethylacetate.

The invention claimed is: 
     
       1. A process for obtaining a crystalline form κ of rifaximin characterized by a powder XRD spectrum with peaks at values of the angle 2θ of 5.3°, 6.8°, 7.8°, 8.5°, 9.3°, 10.1°, 10.3°, 12.1°, 12.7°, 13.4°, 13.7°, 14.6°, 15.3°, 15.8°, 16.4°, 16.9°, 17.7°, 18.0°, 18.8°, 19.2°, 19.7°, 20.3° and 22.1° comprising:
 contacting (i) solid rifaximin, (ii) a solution of rifaximin in ethylacetate, or (iii) a solution of rifaximin in methyl isobutylketone, with ethylacetate to form a second solution of rifaximin; 
 filtering said second solution of rifaximin to obtain a filtered product; and 
 drying the filtered product to obtain said crystalline form κ of rifaximin. 
 
     
     
       2. The process of  claim 1 , wherein said contacting said solid rifaximin or said solutions of rifaximin with ethylacetate occurs at a temperature in the range from 40 to 60° C. 
     
     
       3. The process of  claim 2 , wherein said ethylacetate which contacts said solution is at a temperature of 50° C. 
     
     
       4. The process of  claim 1 , wherein said solution of rifaximin is an ethylacetate solution. 
     
     
       5. An ethylacetate solvated rifaximin crystalline form characterized by a powder X-ray diffraction spectrum with peaks at values of angles 2θ of 5.23°, 6.70°, 7.57°, 8.09°, 8.49°, 8.95°, 11.78°, 12.08°, 13.17°, 14.62°, 14.80°, 15.78°, 16.24°, 16.64°, 19.13°, 21.38°, 23.70°. 
     
     
       6. A process for preparing the ethylacetate solvated rifaximin crystalline form of  claim 5  comprising contacting solid rifaximin or a solution of rifaximin in ethylacetate with ethylacetate to yield a crystalline form of ethylacetated, solvated rifaximin and filtering the crystalline form therefrom.